Nucleic Acids Research, 1983, Vol. 11, No. 22 7743-7758
© 1983
MOLECULAR BIOLOGY |
Cross-linking of DNA induced by chloroethyinitrosourea is prevented by O6-methyiguanine-DNA methyttransferase
Imperial Cancer Research Fund, Mill Hill Laboratories London NW7 IAD, UK
*Present address: University Department of Radiotherapy and Clinical Oncology, Newcastle-upon-Tyne, UK
Received September 26, 1983. Accepted October 21, 1983.
The DNA repair enzyme 06-methylguanine-DNA methyltransferase has been used as a reagent to analyse the initial reaction sites of alkylatlng agents such as chloroethy In itrosourea that cross-link DNA. The transferase can be employed for this purpose because it removes substituted ethyl groups from DNA, as shown by its ability to act on 06-hydroxyethylguanine residues In DNA. The enzyme counteracts the formation of interstrand cross-links Induced by bls-chloroethylnltrosourea, but not those induced by nitrogen mustard. Once formed, chloroethyl-nitrosourea-induced cross-links are not broken by the enzyme. In agreement with deductions from experiments with living cells, it is concluded that chloroethylnitrosoureas act by forming reactive monoadducts at the 06 position of guanine and/or the 04 position of thymine, which subsequently generate -CH2CH2- bridges to the complementary DNA strand. A new method for quantitatlng Interstrand cross-links in DNA has been employed.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Sanada, M. Hidaka, Y. Takagi, T. Y. Takano, Y. Nakatsu, T. Tsuzuki, and M. Sekiguchi Modes of actions of two types of anti-neoplastic drugs, dacarbazine and ACNU, to induce apoptosis Carcinogenesis, December 1, 2007; 28(12): 2657 - 2663. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Hansen, R. Nagasubramanian, S. M. Delaney, L. D. Samson, and M.E. Dolan Role of O6-methylguanine-DNA methyltransferase in protecting from alkylating agent-induced toxicity and mutations in mice Carcinogenesis, May 1, 2007; 28(5): 1111 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Hansen, R. Nagasubramanian, S. M. Delaney, M. M. Cherian, S. Lin, S. C. Kogan, and M. E. Dolan Role of O6-Alkylguanine-DNA Alkyltransferase in Protecting against 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU)-Induced Long-Term Toxicities J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1247 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Kreklau, M. Limp-Foster, N. Liu, Y. Xu, M. R. Kelley, and L. C. Erickson A novel fluorometric oligonucleotide assay to measure O 6-methylguanine DNA methyltransferase, methylpurine DNA glycosylase, 8-oxoguanine DNA glycosylase and abasic endonuclease activities: DNA repair status in human breast carcinoma cells overexpressing methylpurine DNA glycosylase Nucleic Acids Res., June 15, 2001; 29(12): 2558 - 2566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Shiraishi, K. Sakumi, and M. Sekiguchi Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase Carcinogenesis, October 1, 2000; 21(10): 1879 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Kreklau, C. Kurpad, D. A. Williams, and L. C. Erickson Prolonged Inhibition of O6-Methylguanine DNA Methyltransferase in Human Tumor Cells by O6-Benzylguanine In Vitro and In Vivo J. Pharmacol. Exp. Ther., December 1, 1999; 291(3): 1269 - 1275. [Abstract] [Full Text]
|
|
|
|
 |
|
 D. M. Kokkinakis, R. C. Moschel, A. E. Pegg, and S. C. Schold Eradication of Human Medulloblastoma Tumor Xenografts with a Combination of O6-Benzyl-2'-deoxyguanosine and 1,3-Bis(2-chloroethyl)-1-nitrosourea Clin. Cancer Res., November 1, 1999; 5(11): 3676 - 3681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Fischhaber, A. S. Gall, J. A. Duncan, and P. B. Hopkins Direct Demonstration in Synthetic Oligonucleotides that N,N'-Bis(2-chloroethyl)-nitrosourea Cross-Links N1 of Deoxyguanosine to N3 of Deoxycytidine on Opposite Strands of Duplex DNA Cancer Res., September 1, 1999; 59(17): 4363 - 4368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J. Glassner, G. Weeda, J. M. Allan, J. L.M. Broekhof, N. H.E. Carls, I. Donker, B. P. Engelward, R. J. Hampson, R. Hersmus, M. J. Hickman, et al. DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents Mutagenesis, May 1, 1999; 14(3): 339 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K. Hansen, W. A. Deutsch, A. Yacoub, Y. Xu, D. A. Williams, and M. R. Kelley Creation of a Fully Functional Human Chimeric DNA Repair Protein. COMBINING O6-METHYLGUANINE DNA METHYLTRANSFERASE (MGMT) AND AP ENDONUCLEASE (APE/REDOX EFFECTOR FACTOR 1 (Ref 1)) DNA REPAIR PROTEINS J. Biol. Chem., January 9, 1998; 273(2): 756 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Chinnasamy, J. A. Rafferty, I. Hickson, J. Ashby, H. Tinwell, G. P. Margison, T. M. Dexter, and L. J. Fairbairn O6-Benzylguanine Potentiates the In Vivo Toxicity and Clastogenicity of Temozolomide and BCNU in Mouse Bone Marrow Blood, March 1, 1997; 89(5): 1566 - 1573. [Abstract] [Full Text] [PDF]
|
|